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Pathogenesis of Lassa fever in cynomolgus macaques.

Hensley LE, Smith MA, Geisbert JB, Fritz EA, Daddario-DiCaprio KM, Larsen T, Geisbert TW - Virol. J. (2011)

Bottom Line: Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Virology, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.

ABSTRACT

Background: Lassa virus (LASV) infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates.

Methods: Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.

Results: Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17). Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.

Conclusion: The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

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Related in: MedlinePlus

Plasma and organ titers. Mean Lassa infectivity of cynomolgus monkey plasma (top panel) and tissue homogenates (10% wt/vol) (bottom panel). LNode = lymph node.
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Figure 4: Plasma and organ titers. Mean Lassa infectivity of cynomolgus monkey plasma (top panel) and tissue homogenates (10% wt/vol) (bottom panel). LNode = lymph node.

Mentions: The onset of plasma viremia occurred in four of six (4/6) animals on day 3 and in all animals (6/6) by day 5.5. Peak viremia (mean 5.0 log10 pfu/ml) occurred on day 13.5 (Figure 4). Infectious LASV was detected in all tissues except the pancreas of all day 7 animals (3/3) (Figure 4). The highest mean LASV titers at day 7 were detected in spleen and lymph nodes (6.3-7.0 log10 pfu/g) (Figure 4) suggesting that these organs are early sites of viral replication. By terminal time points (days 13.5-17) virus was detected in all tissues of all three terminal animals. The highest mean titers from these terminal animals were documented in the liver (7.7 log10 pfu/g), followed by adrenal gland (7.2 log10 pfu/g), and spleen (6.9 log10 pfu/g) (Figure 4).


Pathogenesis of Lassa fever in cynomolgus macaques.

Hensley LE, Smith MA, Geisbert JB, Fritz EA, Daddario-DiCaprio KM, Larsen T, Geisbert TW - Virol. J. (2011)

Plasma and organ titers. Mean Lassa infectivity of cynomolgus monkey plasma (top panel) and tissue homogenates (10% wt/vol) (bottom panel). LNode = lymph node.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104370&req=5

Figure 4: Plasma and organ titers. Mean Lassa infectivity of cynomolgus monkey plasma (top panel) and tissue homogenates (10% wt/vol) (bottom panel). LNode = lymph node.
Mentions: The onset of plasma viremia occurred in four of six (4/6) animals on day 3 and in all animals (6/6) by day 5.5. Peak viremia (mean 5.0 log10 pfu/ml) occurred on day 13.5 (Figure 4). Infectious LASV was detected in all tissues except the pancreas of all day 7 animals (3/3) (Figure 4). The highest mean LASV titers at day 7 were detected in spleen and lymph nodes (6.3-7.0 log10 pfu/g) (Figure 4) suggesting that these organs are early sites of viral replication. By terminal time points (days 13.5-17) virus was detected in all tissues of all three terminal animals. The highest mean titers from these terminal animals were documented in the liver (7.7 log10 pfu/g), followed by adrenal gland (7.2 log10 pfu/g), and spleen (6.9 log10 pfu/g) (Figure 4).

Bottom Line: Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Virology, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.

ABSTRACT

Background: Lassa virus (LASV) infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates.

Methods: Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.

Results: Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17). Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.

Conclusion: The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

Show MeSH
Related in: MedlinePlus